Unit 9 - 4 Biochemistry

Front 1

how is ATP generated

Back 1

oxidation of fuel molecules

glucose
amino acids and fa during fasting

Front 2

common intermediate in all oxidation reactions

Back 2

acetyl-CoA; jumps into citric acid cycle; the carbons are released as C02

when were losing weight we're really blowing it off as C02 into the atmosphere

Front 3

electrion carriers in the oxidation reactions

Back 3

NADH/FADH2 via ETC, to 02 (form H20)

Front 4

major electron dor in reductive biosynthesis

Back 4

NADPH; supplies electrons to biosynthetic reactions

Front 5

succinate

Back 5

can be used for synthesis of AA and heme; example of building block with multiple roles in biosynthesis

Front 6

when do you see allosteric interactions/regulation

Back 6

first commited step of a pathway

these reactions are very fast and allow pathways to respond very quickly

(covalent modifications are longer term)

Front 7

when do you see covalent modification

Back 7

phosphorylation/dephosphorylation

Front 8

adjustment of enzyme levels

Back 8

HMG-CoA redutacse; cholesterol biosynthesis

these enzymes are upregulated by sterol regulatory element binding proteins

Front 9

compartmentalization

Back 9

cytosol vs mitochondria; location of a substrate determines what it is used for

Front 10

mitochondrial acetyl CoA uses vs cytosol

Back 10

cytosol: FA synthesis

mitochondrial: ketone body syntehsis, or energy production via TCA

Front 11

mitochondrial fatty acids go where

Back 11

degradation via b oxidation

Front 12

cytosol fatty acids go where

Back 12

esterified; put into tg; released

Front 13

glucose 6 phosphatase

Back 13

not present in muscle; once glucose is in muscle its phosphoryalted and stays there

Front 14

why does muscle not have glucagon receptors

Back 14

bc it does not regulate blood sugar levels so it doesnt have glucagon receptors; liver does this and thus has receptors

Front 15

insulin release

Back 15

glycogen synthesis; fa synthesis; tg synthesis; liver glycolysos

Front 16

glucagon release

Back 16

glycogenolysis; gluconeogenesis; lipolysis, decreasd liver glycolysis

Front 17

primary role of glucagon

Back 17

upregulate glucose expression

Front 18

primary role of insulin

Back 18

takes glucose out of blood and stores it as glycogen or converts glucose to fatty acids

Front 19

preferred fuel for brain

Back 19

glucose; brain cant use fatty aids (bc cant cross blood brain barrier, bound to albumin)

can use some ketonebodies

Front 20

immediate reserve of glucose

Back 20

liver glycogen

Front 21

what can muscles and other tissues be converted to

Back 21

glucose

Front 22

can fatty acids be converted to glucose?

Back 22

no! fatty acids broken down to acetyl-CoA and once this enteres the TCA cycle it goes off as C02

can only use amino acids, pyruvate, and lactate and so on to produce glucose

Front 23

harmful effects of hyperglycemia

Back 23

1. osmotic effects - dehydration, polyuria, polydypsia; draw water out of tissues, dehydrates, brain doesnt function well
2. glycation of proteins (glucose switches between ring form and aldehyde which is reactive; high levels of glucose predispose proteins to glycation; nonenzymatic reactions where glucose cross links proteins by binding nitrogenous groups; cross linked proteins also become neoantigens)
3. free radical damage of B-cells (these cells sense glucose in environment; through ox phosphorylation they release insulin; they rely exclusively on ox phos to trigger insulin release; sustained high glucose levels causes free radical damage w ROS produced in mitochondria
3. free radical damage of B-cells

Front 24

GLUT2R

Back 24

low affinity transporters; bidirectional in liver

Front 25

hepatic fat synthesis

Back 25

glucose into liver via GLUT2 -> glycolysis to pyruvate -> mitochondrial conversion of pyruvate to OAA (pyruvate carboxylase) and acetyl CoA (pyruvate dehydrogenase) to make citrate -> transported into cytoplasm via citrate shufttle -> converted back to acetyl CoA -> malonyl CoA (adding another C02 using biotin) -> fatty acid synthase knows hwen you're gotten up to 16 and chops it off which releases as palmitate -> estified to TG -> heads out into blood

Front 26

what closes the K channel in b islet cells

Back 26

ATP

Front 27

what triggers voltage gated Ca channel in B islet cells to open

Back 27

closing of K channels by ATP

calcium binds synaptotagmin allows vesicular fusion; exocytosis of insulin

Front 28

MODY 2

Back 28

maturity onset diabeties of the young; whole family of MODYs; mc oen is a defect in glucokinase

mutations that increases Vmax of glucokinase leads to MODY: leadst o insufficient insulin release;

Front 29

MELAS

Back 29

mitochondrial diseases in B islet cells; cant

Front 30

PNDM

Back 30

persistent neonatal diabetes mellitus; mutation in K channel where it is inresponsive to ATP so open all the time, no insulin release

Front 31

insulin signaling

Back 31

dimer receptor; binds to insulin which induces conformational change in receptor leads to activation of tyrosine kinase domains; cross phosphorylate one another; phosphorylates IRS-1 (insulin receptor substrate 1 = linker protein); attracts PIP2 -> PIP3 -> activates PDK1 (cytosoliic protein which is attracted to PIP3) -> leads to dephosphorlation of enzymem targets

sum = insulin actiavtes signaling cascade which leads to pleotropic response (multiple consequences across many enzymes via phosphorylationdephorphorylation cacade); think of target DEPHORPHORYLATION when you think of insulin

glucagon = target dephorphorylation

Front 32

insulin signaling

Back 32

dimer receptor; binds to insulin which induces conformational change in receptor leads to activation of tyrosine kinase domains; cross phosphorylate one another; phosphorylates IRS-1 (insulin receptor substrate 1 = linker protein); attracts PIP2 -> PIP3 -> activates PDK1 (cytosoliic protein which is attracted to PIP3) -> leads to dephosphorlation of enzymem targets

sum = insulin actiavtes signaling cascade which leads to pleotropic response (multiple consequences across many enzymes via phosphorylationdephorphorylation cacade); think of target DEPHORPHORYLATION when you think of insulin

glucagon = target dephorphorylation

Front 33

tyrosine kinase domains

Back 33

cytoplasmic side of insulin receptor

Front 34

tyrosine kinase domains

Back 34

cytoplasmic side of insulin receptor

Front 35

what jumps out at you looking at the allosteric enzymes in glycoegen and TAG synthesis in liver

Back 35

AMP/ATP ratio plays a role inr egulating activity of phosphofructokinase

low energy stimulates it for glycolysis
high energy inhibits glycolysis

dont need to create more aTP if youve got enough

Front 36

where deos citrate feed back on?

Back 36

PFK1

Front 37

fructose 2,6bisP

Back 37

can override the AMP/ATP level regulation of phosphofructokinase-1

Front 38

where does alanien come from

Back 38

anarobic metabolism of muscles; alanine is the pyruvate analog of amino acids

alanine -> pyruvate to stimualte gluconeogensis (alanine inhibits PEP -> pyruvate so the PEP can go into gluconeogenesis)

Front 39

liver version of hexokinase

Back 39

glucokinase; pancreas also has this

Front 40

difference ine nzyme activity between hexokinase and glucosekinase based on glucose levels

Back 40

at physiological glucose levels hexokinase is maxed out; however the liver/pancreatic enzyme glucokinase is lower at normal serum glucose concentrations;

compare the two curves to the oxygen dissociation curve; net flux of oxygen from myoglobin-> hemoglobin; the analogy is that youre going to have a net flux of glusose in your liver to your periphery; the hexokinase in muscles are good at locking in sugars (net flux away from liver)

Front 41

which kinase is not inhibited by its product

Back 41

hexokinase is inhibited (mops up extra glucose to get it into tissues asap)

glucokinase is not inhibited by its product

Front 42

futile cycle

Back 42

during fasting state (low glucose) glucokinase is stored in nucleus of liver by a regulatory protein GKRP; when you have elevated glucose kinase is transported into liver, released by regulatory protein, increases synthesis of G6P

you minimize the futile cycle using the binding/releasing of glucokinase

Front 43

which molecule does phosphofructokinase-1, F16BP1 look like?

Back 43

hemoglobin

dont need allosteric site right next to effector site to effect it

Front 44

F26BP increases the affinity of PFK 1for F6P

Back 44

there is also an antagonistic effect between ATP and F26BP

so even though cell energy levels are high PFK-2 tempers the activity of the enzyme;

even though we have lots of energy keeps signal on for glycolysis to create ATP or store as fat

Front 45

alanine is the amino acid homologue of what

Back 45

pyruvate

thus alanine is the negative allosteric regulatic of pyruvaet kinase; blocks glycolysis; stimulates gluconeogenesis

Front 46

cofactor for pyruvate carboxylase

Back 46

biotin

Front 47

what happens to NADPH producing enzymes during the fed state

Back 47

upregulation

PPP is upregulated (need NADPH); malic enzymes and glucose 6 phosphate dehydrogenase

Front 48

fate of glucose in the liver

Back 48

NADH level in mitochondria start to increase; burning glucose increases NADH which feeds back, inhbits isocitrate dehydrogenase which accumulates citrate in tCA cycle; feeds back to inhibit PFK1 to ensure glycogen stores are renewed

insulin activates F26BP; fires carbons into mitochondria; fat synthesis for energy storage in adipocytes

Front 49

if adipocytes were resistant to insulin

Back 49

would not produce enough adipoprotein lipase; the freshly packed VLDLs and chylomicrons would thus not be degraded and not net important of fatty acids; this is why people w metabolic syndrome in diabetes have resistance to the importation of fatty acids into cell

Front 50

hepatic fructose handling

Back 50

fructose handling in liver vs glucose

fructose bypasses regulatory steps of glycolysis;

Front 51

amp kinase

Back 51

master regulator of intracellular homeostasis; metformin actives AMP kinase through inhibition of AMP deaminase

Front 52

bile salts

Back 52

amphipathic; surround triglycerides to form micelles; increased area enhances digestion by pancreatic lipase

Front 53

breakdown of dietary triglycerides

Back 53

pancreatic lipase; produces two fatty acid molecules and one molecule of 2-monoacylglycerol; these products stick on micelles prior to absorption

Front 54

phospholipases

Back 54

recognize and hydrolyze specific bonds in a phospholipid

Front 55

cholesterol esterase

Back 55

removes the fatty acid groupf rom cholesterol; decreases the hydrophobicity of cholesterol

Front 56

where does synthesis of apo B-48 occur

Back 56

rough ER

TG formation in smooth ER

chylomicron assembly in ER and golgi

Front 57

microsomal triacylglycerol transfer protein (MTTP)

Back 57

required for assembly of chylomicrons and VLDL (apoB100/48); cant export fats; accumulate in cells = abetalipoproteinemia

Front 58

microsomal triacylglycerol transfer protein (MTTP)

Back 58

required for assembly of chylomicrons and VLDL (apoB100/48); cant export fats; accumulate in cells = abetalipoproteinemia

Front 59

abetalipoproteinemia

Back 59

MTTP deficiency; cant export fats; accumulate in cells; deficiency in apoB100 and 48; symptoms appear in first few months of lfie; intestinal biopsy shows accumulation within enterocytes s ince cant export as chylomicrons

Front 60

abetalipoproteinemia

Back 60

MTTP deficiency; cant export fats; accumulate in cells; deficiency in apoB100 and 48; symptoms appear in first few months of lfie; intestinal biopsy shows accumulation within enterocytes s ince cant export as chylomicrons

Front 61

infant with failure to thrive, steatorrhea, acanthocytosis, ataxia, night blindness

Back 61

abetalipoproteinemia; deficiency in microsomal triacylglycerol transfer protein;

fat soluble vitamin deficiency

Front 62

infant with failure to thrive, steatorrhea, acanthocytosis, ataxia, night blindness

Back 62

abetalipoproteinemia; deficiency in microsomal triacylglycerol transfer protein;

fat soluble vitamin deficiency

Front 63

ApoE

Back 63

mediates Extra (remnant) uptake in liver, hepatic receptors recognize it

Front 64

ApoC-II

Back 64

cofactor for lipoprotein lipase; found on capillary endothelial cells (muscle/adipose)

Front 65

lipoprotein lipase (LPL)

Back 65

degradation of TG circulating in chylomicrons and VLDLs; directs FA into muscle and adipose tissue; recognizes ApoCII on chylomicrons

Front 66

cfamilial hylomicronemia

Back 66

elevated chylomcirons and VLDL; xanthomas, hepatosplenomegaly and pancreatitis

Front 67

xanthomas, hepatosplenomegaly and pancreatitis

Back 67

familial chylomicronemia; no LPL to recognize CII on chlomicrons to degrade TG

Front 68

carnitine-palmitoyl transferase I and II deficiency

Back 68

required to move acyl-coa (fatty acid) from cytoplasm through inner mitochondrial membrane; deficiency = inability to transport LCFA into the mitochondria resulting in toxic acumulation. Causes weakness, hypotonia and hypoketotic hypoglycemia

Front 69

hypoketotic hypoglycemia

Back 69

carnitine deficiency (cant transport LCFA through inner mitochondrial membrane

Front 70

LDL

Back 70

IDL with TG removed in liver; transports cholesterol to peripheral tissue

Front 71

VLDL

Back 71

transports TG from liver to peripheral tissue

Front 72

IDL

Back 72

degraded VLDL; delivers TG and cholesterol to liver, where the TG is removed and it forms LDL

Front 73

Apo C-II location

Back 73

chylomicrons, VLDL

cofactor for LPL

Front 74

Apo A-1 location/function/deficiency

Back 74

HDL

cofactor for LCAT

deficiency = corneal opacities

Front 75

super young pt with atherosclerosis, super high cholesterol, xanthamos on achilles, etc

Back 75

hypercholesterolemia; defective LDL receptors; can't internalize LDL so it is very high in tissues

Front 76

tangiers disease

Back 76

uences of the liability